Probiotics for the Management of Liver Cirrhosis and Its Complications.

Cirrhosis is the terminal stage of various chronic liver diseases, and its decompensated stage is mainly characterized by serious complications, such as hepatic encephalopathy, ascites, spontaneous bacterial peritonitis, and gastrointestinal bleeding. Gut microbial dysbiosis is prevalent in patients with cirrhosis. Considering the bidirectional regulation of the gut-liver axis, dysbiosis is closely related to the development and progression of liver cirrhosis.

Study on the adjuvant activity and mechanism of action of a novel Monophosphoryl Lipid A.

In order to develop a novel vaccine adjuvant that is highly efficient, cost-effective, and suitable for widespread application, this study employed synthetic biology techniques to produce a new type of Escherichia coli monophosphate lipid A (N-MPL). Specifically, the phosphate group attached to the C-1 position was removed, and a hydroxyl group was introduced into the 3'-secondary fatty acid chain of the original lipid A structure. This modification aimed to reduce toxicity while enhancing water solubility.

Exploring the alleviating effect and mechanism of the diterpenoid alkaloid Polyschistine D on rheumatoid arthritis based on network pharmacology and non-targeted metabolomics.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease. The pathogenesis is complex, and the pathological manifestations are mainly articular cartilage and bone injury, synovial destruction, pannus hyperplasia and inflammatory cell infiltration. Polyschistine D (PD) is a natural active product derived from the Chinese herbal medicine Aconitum pendulum Busch.

Harmine derivative ZLWH-38 ameliorates the therapeutic efficacy of colistin against XDR-Ab pneumonia by suppressing inflammatory responses.

Background: Acinetobacter baumannii (Ab), especially extensively drug-resistant Ab strains (XDR-Ab), poses a significant threat to clinical medicine due to its high mortality rate and limited treatment options. Harmine derivatives exhibit potent anti-inflammatory and immunomodulatory effects. In this study, we aimed to investigate whether the harmine derivative ZLWH-38 combined with colistin could enhance therapeutic efficacy against XDR-Ab pneumonia by suppressing inflammatory responses.

Nanogel-Engineered Drug Delivery Systems for Enhanced Ocular Therapeutics.

Despite the growing global burden of ocular disorders, conventional ophthalmic formulations remain limited by inadequate bioavailability, rapid clearance, and poor corneal penetration, necessitating frequent dosing and compromising efficacy. This review highlights the revolutionary potential of nanogels, which integrate the advantages of nanoparticles and hydrogels, as advanced ocular drug delivery systems. Through structural engineering and advanced preparation techniques, nanogels achieve enhanced corneal retention, superior mucoadhesion, and controlled drug release.

[A new cephalotaxine-type alkaloid dimer from Cephalotaxus lanceolata].

The chemical constituents from Cephalotaxus lanceolata were isolated and purified by using multiple chromatographic techniques, including octadecylsilane(ODS), silica gel, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography(HPLC). A total of 17 compounds obtained were identified by using spectroscopic methods such as nuclear magnetic resonance(NMR), mass spectrometry(MS), and ultraviolet(UV) combined with literature data. Compound 1 was a new alkaloid dimer, named cephalancetine E.

[Metabolites and anti-inflammatory activities of Monascus sanguineus].

A variety of chromatographic techniques, including silica gel, ODS, Sephadex LH-20, and HPLC, were employed to isolate and purify the fermentation products of rice with Monascus sanguineus. A total of 38 compounds were isolated, and their structures were identified by UV, IR, NMR, MS, calculated ECD, and comparison with literature data. Compounds 1-4 were identified as new natural products, and other compounds were isolated from this fungus for the first time.

[Characterization of hippocampal components of Danzhi Xiaoyao Formula based on HPLC-Q-TOF-MS/MS and network pharmacology and assessment of its therapeutic potential for nervous system diseases].

In this study, the pharmacodynamic components and potential pharmacological functions of Danzhi Xiaoyao Formula in treating nervous system diseases were investigated by hippocampal component characterization and network pharmacology. After rats were administrated with Danzhi Xiaoyao Formula by gavage, high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS) was employed to explore the components in the hippocampus of rats. Fifty-seven components were identified in the hippocampus of rats by comparing the extract of Danzhi Xiaoyao Formula, herbal components in the hippocampus after administration, and blank samples.

Bioactive Silk Fibroin Hydrogel Harnesses BMSCs-EVs to Modulate Inflammatory Microenvironment in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a common age-related disorder associated with inflammation, pain and impaired mobility. In this study, we developed a therapeutic system using silk fibroin (SF) hydrogel loaded with mRNA-engineered extracellular vesicles derived from murine bone marrow mesenchymal stem cells (BMSCs-EVs) to modulate macrophage polarization and alleviate IVDD. BMSCs were isolated from 6-week-old C57BL/6 mice, and an acute IVDD model was established via 18G needle puncture of the coccygeal discs (Co7-Co10).

Pulsatile sequential drug release system for cascade tumor deep penetration and differentiation therapy to enhance chemoimmunotherapy.

Cancer stem cells (CSCs) and myeloid-derived suppressor cells (MDSCs) contribute to chemoresistance and immunosuppression, constraining chemoimmunotherapy outcomes. Differentiation therapy, aiming to mature CSCs and MDSCs, shows great promise. However, its efficacy is hindered by limited accessibility in hypoxic deep tumor regions.

Measuring the medication literacy level of community residents: a cross-sectional study.

Objective: To assess the current status and identify factors influencing the medication literacy level of community residents, providing a scientific basis to enhance medication literacy and effectively promote the safe use of medications.

Methods: A questionnaire survey was conducted among 2,008 community residents in Shenzhen, employing economic stratification and proportionate sampling methods. The analysis utilized various statistical methodologies, including T-tests, F-tests, multiple linear stepwise regression, and structural equation modeling to assess the current medication literacy status and the factors influencing it.

Complete genome sequences of strains Y and N, capable of conjugated diene biohydrogenation.

We report the complete genome sequences of two acetogenic strains, Y and N, isolated from river sediment. Under anaerobic acetogenic conditions, strain Y biohydrogenates isoprene, while strain N transforms 1,3-butadiene to 1-butene.

Metabolite Profiling of Guipi Pill Using UHPLC-Q-Orbitrap-HRMS and Determination of the Pharmacokinetics of its Major Prototype Components.

Guipi Pill (GPP), a classic traditional formula used to treat anxiety disorders, demonstrates significant pharmacological activity. However, research on its pharmacodynamic material basis remains limited. UHPLC-Q-Orbitrap-HRMS was used to systematically analyze the metabolites of GPP in the blood, urine, bile, and feces of rats after oral administration and elucidate its in vivo metabolic processes.

Engineered Fusion Enzyme-Mediated Non-Consecutive Cyclization-Glycosylation Enables Heterologous Synthesis of Antifungal Enfumafungin.

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, constitute a distinct class of fungi-derived fernane-type triterpenoids renowned for their potent antifungal activity. Notably, ibrexafungerp, a semi-chemically synthesized analogue of enfumafungin, has recently received approval as a novel antifungal drug. Thus, reconstituting the heterologous biosynthesis of enfumafungin holds great significance, as it offers a promising route for high-level production.

MRI-based radiomics predicts complete responses to initial transcatheter arterial chemoembolization in virus-associated early and intermediate stage HCC.

To evaluate the value of a multiparametric MRI-based nomogram on predicting response to transcatheter arterial chemoembolization (TACE) in virus-associated hepatocellular carcinoma (HCC) patients; METHODS: This study enrolled 235 and 51 patients from Center 1 and 2, respectively. All patients underwent baseline MRI scans before treatment. The least absolute shrinkage and selection operator (LASSO) regression method was used to screen radiomics features from intra- and peri-tumor areas to establish the radiomics signatures (RS).

In vitro identification and in vivo metabolic profiling of chemical constituents in seeds.

seeds (MOS), recognized as a nutritionally valuable food, are rich in diverse bioactive compounds and widely utilized for disease prevention and adjunctive therapy. However, their in vitro chemical constituents and in vivo blood-absorbed/metabolized components remain underexplored. This study pioneered the application of UPLC-Q-Exactive Orbitrap-MS to characterize MOS-derived compounds in vitro and in vivo, concurrently elucidating major constituents' fragmentation pathways via mass spectrometry.

Effect of semaglutide on arrhythmic, major cardiovascular, and renal outcomes in patients with overweight or obesity: a systematic review and meta-analysis.

Background: Semaglutide has demonstrated potential in controlling hyperglycemia and lowering cardiovascular (CV) risk. However, its impact on arrhythmic, major CV, and renal outcomes is not well-defined. This systematic review and meta-analysis aimed to assess these effects in patients with overweight or obesity.

Development of and neutralization assays for New World alphaviruses based on the VSV pseudovirus system.

The New World alphaviruses, including Eastern Equine Encephalitis Virus (EEEV), Western Equine Encephalitis Virus (WEEV), and Venezuelan Equine Encephalitis Virus (VEEV), are known to cause neurological diseases that pose a significant threat to public health concerns and bioterrorism preparedness challenges due to their potential for aerosol transmission. Currently, no FDA-approved vaccines or antiviral drugs are available for humans, although ongoing studies are exploring potential solutions. Most vaccine evaluation methods rely on live virus models, which require handling in biosafety level 3 (BSL-3) facilities.

C steroidal glycosides from Cynanchum paniculatum (Bunge) Kitagawa: structural elucidation and biological evaluation.

Phytochemical investigation of the ethyl acetate-soluble fraction from the 95 % ethanol extract of Cynanchum paniculatum (Bunge) Kitagawa roots and rhizomes led to the isolation of eight previously undescribed C steroidal glycosides (1-8) designated cynapanosides H-O, alongside eighteen known analogues. The structures of the compounds were elucidated by comprehensive spectroscopic analysis using HRESIMS, 1D/2D NMR, and comparison with reported data. All isolated glycosides were evaluated for cytotoxic activity against HeLa and HepG2 cell lines.

An enhanced bioluminescent probe for in vivo imaging of drug-induced apoptosis via acetylcholinesterase targeting.

Acetylcholinesterase has emerged as a compelling biomarker for optical imaging of tissue apoptosis. Existing AChE-targeted imaging approaches rely heavily on fluorescent probes, whose performance is often hindered by autofluorescence, light scattering, phototoxicity, photobleaching, and limited in vivo accuracy. Bioluminescence imaging, an intrinsic light-emitting modality that requires no external excitation, overcomes these limitations while offering superior sensitivity and applicability in living systems.

Tunable Site Selectivity and Chemo- and Regioselectivity: Diversification of Indole Alkaloid Privileged Scaffolds Enabled by λ-Iodane-Mediated Cross-Nucleophile Coupling Cascade.

Amidst nature's repertoire of small molecule architectures, indole alkaloid-derived privileged scaffolds continuously support innovation in bioactive compound discovery and propel fragment-based drug design. Herein, we realized a metal-free, site-selective, and chemo- and regioselective cross-nucleophile coupling cascade of pluripotent indole-enamine-aniline intermediates by use of λ-iodane-mediated umpolung chemistry. The protocol is applicable toward the divergent synthesis of valuable benzo[]indolo[3,2-][2,6]naphthyridines and azepino[4,5-]indoles, which are very important privileged scaffolds in communesin-, peroforamidine-, and iboga-type alkaloids.

Site-specific engineering of S-Te-S bridged nano-prodrug: A dual equilibrium strategy for enhanced antitumor efficacy and safety of paclitaxel.

Homodimeric prodrug nanoassemblies (HPNs) have emerged as an effective strategy to enhance the therapeutic efficacy and safety of chemotherapeutic drugs. However, achieving both stable assembly and rapid drug release in tumor remains a critical challenge. Herein, we designed S-Te-S linkages with varying linkage lengths (α-, β-, and γ-) to develop three paclitaxel (PTX) homodimeric prodrug nanoassemblies (PHPNs).

Targeting hematopoietic progenitor kinase 1 (HPK1) for tumor immunotherapy: advances in small molecule inhibitors.

Hematopoietic progenitor kinase 1 (HPK1), also known as MAP4K1, is a hematopoietic-specific serine/threonine kinase and a member of the MAP4K family of mammalian Ste20-associated protein kinases, which share a highly similar protein structure, and play important roles in the regulation of cell survival, cell migration, apoptosis and autophagy. HPK1 is a negative regulator of T-cell, B-cell and dendritic cell-mediated immune responses, and HPK1 kinase deficiency increases cytokine secretion and enhances T-cell signaling, viral clearance and tumor growth inhibition. Thus, HPK1 may be implicated in the development and progression of human malignant tumors and is a potent target for anti-tumor immunotherapy.

A comprehensive quality control system for Chinese herbal medicine based on HPLC ratio quantitative fingerprinting and spectral quantized fingerprinting combined with antioxidant activity: A case of Siegesbeckiae Herba.

A reliable quality control system is crucial to ensure the quality consistency, clinical efficacy, and safety of Chinese herbal medicines (CHMs) and their preparations. Herein, high performance liquid chromatography (HPLC) five-wavelength fusion fingerprint (FWFFP) and its ratio quantitative fingerprint (ROFP) were established, with the innovative ratio systematically quantitative fingerprint method (RSQFM) applied for quality assessment. The 22 batches of Siegesbeckiae Herbas (SHs) were classified into six Grades (0.